Thomas M. Roberts, PhD
Office phone: 617-632-3049
Email: firstname.lastname@example.org .edu
Preferred contact method: email
Area of Research
Signaling Mechanisms and Cancer
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Dr. Roberts received his PhD in 1976 from Harvard University, where he also completed a postdoctoral fellowship. In 1981, he joined the DFCI faculty. Dr. Roberts has played a seminal role in discovering the conceptual fabric of signaling downstream from tyrosine kinases. His lab and that of Lewis Cantley, working together, pioneered research on PI3 kinase. He has extended his work to stimulate the discovery of clinically useful inhibitors of oncogenic kinases.
ResearchSignaling Mechanisms and Cancer
Through the process of signal transduction, cells communicate what is happening on their surfaces to the regulatory machinery inside. This process is facilitated by a class of enzymes called kinases, which help activate specific genes in the long strands of DNA in a cell's nucleus. An overactive kinase can lead to an overactive gene and, ultimately, to cancer. Our laboratory is researching the role of these catalysts of cell growth and division and has discovered how several work. Our discoveries have become the basis of new drugs that target the actions of specific kinases. This class of drugs, called kinase inhibitors, offers extraordinary hope for the future of cancer care.
Research in the laboratory currently focuses on three areas. One is how particular kinases are involved in cancer. For instance, the kinase termed PI3K blocks the orderly process of cell death, called apoptosis. Thus, inhibiting PI3K should lead to tumor cell death. We are also exploring new ways to measure kinase activity in tumors. Every tumor is unique, with its own pattern of activated kinases. Because there are more than 600 different kinases in a given tumor, it is important to find which ones are activated so that we know which ones to inhibit. Finally, our laboratory is developing murine model systems to study kinases in tumors.
Once kinases have been pinpointed, our laboratory develops the techniques and technology that allow pharmaceutical companies to make new drugs that target them. We supply the company with the reagents necessary to test the effect of drugs on the action of tyrosine kinases. In addition, DFCI scientists have developed the means to make kinases for testing. This collaboration has led to the creation of several new drugs. In particular, the drug Gleevec has been approved by the FDA against chronic myeloid leukemia (CML). More recently we have been working with Novartis on PI3k inhibitors. PI3K inhbitors from Novartis and other companies are now entering Phase 2 trials.
- Whitman M, Kaplan DR, Schaffhausen B, Cantley L, Roberts TM (1985). Association of phospha-tidylinositol kinase activity with polyoma middle-T competent for transformation. Nature 315: 239-42.
- Kaplan DR, Whitman M, Schaffhausen B, Pallas DC, White M, Cantley L, Roberts TM (1987). Common elements in growth factor stimulation and oncogenic transformation: 85 kD phosphoprotein and phosphatidylinositol kinase activity. Cell 50:1021-9.
- Piwnica-Worms H, Saunders KB, Roberts TM, Smith AE, Cheng SH (1987). Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell 49: 75-82.
- Druker BJ, Mamon HJ, Roberts TM (1989). Oncogenes, Growth Factors, and Signal Transduction. New England Journal of Medicine 321: 1383-91.
- Varticovski L, Druker B, Morrison D, Cantley L, and Roberts T (1989). The colony stimulating factor-1 receptor associates with and activates phosphatidylinositol-3 kinase. Nature 342:699.
- Pallas DC, Shahrik LK, Martin BL, Jaspers S, Miller TB, Brautigan DL, Roberts and TM (1990). Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A. Cell 60:167.
- Wood K, Roberts T, Blenis K (1992). ras mediates nerve growth factor receptor modulation of three signal-transducing protein kinases: MAP kinase, Raf-1, and RSK. Cell 68:1041-50.
- Fu H, Xia K, Pallas DC, Cui C, Conroy K, Narsimhan RP, Mamon H, Collier RJ, Roberts TM (1994). Interaction of the Protein Kinase Raf-1 with 14-3-3 Proteins. Science 266: 126-9.
- Pallas DC, Fu H, Haehnel L, Weller W, Collier J, Roberts TM (1994). The 27kDa and 29kDa Polyomavirus Middle Tumor Antigen-Associated Proteins are Members of the 14-3-3 Protein Family. Science 265: 535-7.
- Zhao JJ, Gjoerup OV, Subramanian RR, Cheng Y, Chen W, Roberts TM, Hahn WC (2003). Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase. Cancer Cell 3:483-95.
- Zhao JJ, Cheng H, Jia S, Wang L, Mikami A, and Roberts TM (2006). The p110a isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation. Proc Natl Acad Sci USA 103(44): 16296-300.
- Jia S*, Liu Z*, Zhang S*, Liu P, Lee S, Zhang J, Lee S, Zhang J, Signoretti S, Loda M, and Roberts TM, and Zhao JJ (2008). Essential roles of PI(3)K-p110b in cell growth, metabolism and tumorigenesis Nature 454:776-9. PMCID: PMC2750091.
- Qi HH*, Sarkissian M*, Bhattacharjee A, Gordon B, Lan F, Huarte M, Yaghi NK, Lim H, Brizuela L, Roberts TM# and Shi Y# (2010). The mental retardation gene PHF8 mediates histone H3K9/H4K20 demethylation and regulates zebrafish craniofacial development. Nature 466:503-7. PMCID: PMC3072215.
- Ilic N, Utermark T, Widlund HR, Roberts TM. (2011) PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis. Proc Natl Acad Sci U S A. Aug 29. Epub ahead of print
- Tamara Utermark*, Trisha Rao*, Hailing Cheng, Qi Wang, Sang Hyun Lee, Charles Zhigang Wang, J. Dirk Iglehart, Thomas M. Roberts1, William J. Muller* and Jean J. Zhao* (2012) The p110? and p110? isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis Genes & Development 26(14):1573-86
- Gritsman, Kira, MD, PhD
- Cizmecioglu, Onur, PhD
- Dake (Utermark), Tamara, PhD
- Gao, Xueliang, PhD
- Pores Fernando, Arun, PhD
- Schmit, Fabienne, PhD
- Spangle, Jennifer, PhD
- Xie, Shaozhen, PhD
- Zhang, Jing, PhD
- Tong, Haoxuan, Graduate Student